Aquaporin 1 expression is associated with response to adjuvant chemotherapy in stage�II and III colorectal cancer

Abstract

Aquaporin 1 (AQP1), which functions as a water transporter, is associated with cancer cell proliferation, invasion, metastasis and angiogenesis in numerous types of solid cancer, including colorectal cancer (CRC). The focus of the present study was to address the potential clinical use of AQP1 expression in CRC as a prognostic and predictive biomarker for disease recurrence and therapeutic outcomes. The current study investigated the expression of AQP1 in surgically resected specimens from 268 patients with stage 0-IV CRC. AQP1 expression was positive in 112 (41.8%) patients, and was significantly associated with left-sided tumors (P<0.01) and with aggressive tumor phenotypes, including depth of invasion (P=0.03), lymph node metastasis (P=0.03), lymphatic invasion (P<0.01) and venous invasion (P<0.01). However, AQP1 expression had no significant prognostic effect on disease-free survival (DFS) in patients with stage II and III CRC following curative surgery. In 84 stage II and III patients who were administered 5-fluorouracil-based adjuvant chemotherapy, positive AQP1 expression was associated with an increased DFS rate compared with that of AQP1-negative patients (P=0.05). Additionally, these results identified that receiving adjuvant chemotherapy was not beneficial to patients with AQP1-negative tumors. This suggests that the expression of AQP1 may be a candidate biomarker predictive of response to 5-fluorouracil-based adjuvant chemotherapy following surgery in patients with stage II and III CRC.

Reduced aquaporin-1 transcript expression in colorectal carcinoma is associated with promoter hypermethylation

“…Yoshida et al reported expression in 56 of 120 (46.7%) patients with stage II and III colon cancer [8]. Imaizumi et al reported expression in 112 of 268 (41.8%) patients with stage 0-IV CRC [10]. In the largest study previously reported, Kang et al reported strong positive staining in 298 of 486 patients with stage I-III colon cancer (61.3%) [9].…”

“…There are limited published data comparing AQP1 expression in normal colonic mucosa to CRC. Imaizumi et al reported that AQP1 protein was not detected in the normal epithelial cells but was expressed in 112 of 268 (41.8%) of stage 0 to IV CRC [10]. Mobasheri et al evaluated the relative abundance and distribution of AQP1 protein using immunohistochemistry and quantitative histomorphometric analysis of tissue microarrays.…”

“…Studies comparing AQP1-null and wildtype mice suggest that AQP1 promotes tumour growth by enhancing endothelial cell migration and angiogenesis [7]. Whilst the relevance of AQP1 expression has been investigated in numerous cancer types, only a small number of studies have investigated the prognostic significance of AQP1 protein expression in CRC, and these have yielded conflicting results [8][9][10]. Changes in DNA methylation are frequent, early events in carcinogenesis [11].…”

A Novel Scoring System for Risk Assessment of Elderly Patients With Cytogenetically Normal Acute Myeloid Leukemia Based on Expression of Three AQP1 DNA Methylation-Associated Genes

“…It's worth noting that most studies show that AQP1 gene acts as an oncogene in various solid cancers to promote cancer development (12)(13)(14), whereas only a few studies report AQP1 as a tumor suppressor that inhibits tumor growth (21,58). Recently, Marietta Tan et al also showed that AQP1 was epigenetically downregulated by promoter methylation and was associated with improved prognosis in salivary gland adenoid cystic carcinoma (20).…”

“…facilitates transcellular water transportation (11). AQP1 plays an oncogenic role in many types of solid cancer, including colorectal cancer, breast cancer, bladder cancer (12)(13)(14). Functionally, AQP1 regulates cell proliferation, invasion, metastasis and angiogenesis.…”